scholarly journals Brucella abortus Invasion of Synoviocytes Inhibits Apoptosis and Induces Bone Resorption through RANKL Expression

2013 ◽  
Vol 81 (6) ◽  
pp. 1940-1951 ◽  
Author(s):  
Romina Scian ◽  
Paula Barrionuevo ◽  
Ana María Rodriguez ◽  
Paula Constanza Arriola Benitez ◽  
Clara García Samartino ◽  
...  

ABSTRACTArthritis is one of the most common complications of human active brucellosis, but its pathogenic mechanisms have not been completely elucidated. In this paper, we describe the role of synoviocytes in the pathogenesis of brucellar arthritis. Our results indicate thatBrucella abortusinfection inhibited synoviocyte apoptosis through the upregulation of antiapoptotic factors (cIAP-2, clusterin, livin, and P21/CIP/CDNK1A). In contrast, infection did not change the expression of proteins that have been involved in apoptosis induction such as Bad, Bax, cleaved procaspase 3, CytC, and TRAIL, among others; or their expression was reduced, as occurs in the case of P-p53(S15). In addition,B. abortusinfection induced upregulation of adhesion molecules (CD54 and CD106), and the adhesion of monocytes and neutrophils to infected synoviocytes was significantly higher than to uninfected cells. Despite this increased adhesion,B. abortus-infected synoviocytes were able to inhibit apoptosis induced by supernatants fromB. abortus-infected monocytes and neutrophils. Moreover,B. abortusinfection increased soluble and membrane RANKL expression in synoviocytes that further induced monocytes to undergo osteoclastogenesis. The results presented here shed light on how the interactions ofB. abortuswith synovial fibroblasts may have an important role in the pathogenesis of brucellar arthritis.

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Johanna Patricia Daily

ABSTRACT The most advanced vaccine against Plasmodium falciparum malaria, RTS,S/AS01, provides partial protection in infants and children living in areas of malaria endemicity. Further understanding its mechanisms of protection may allow the development of improved second-generation vaccines. The RTS,S/AS01 vaccine targets the sporozoites injected by mosquito vectors into the dermis which then travel into the blood stream to establish infection in the liver. Flores-Garcia et al. (Y. Flores-Garcia, G. Nasir, C. S. Hopp, C. Munoz, et al., mBio 9:e02194-18, 2018, https://doi.org/10.1128/mBio.02194-18) shed light on early protective responses occurring in the dermis in immunized animals. They demonstrated that immunization impairs sporozoite motility and entry into blood vessels. Furthermore, they established that challenge experiments performed using a dermal route conferred greater protection than intravenous challenge in immunized mice. Thus, the dermal challenge approach captures the additional protective mechanisms occurring in the dermis that reflect the natural physiology of infection. Those studies highlighted the fascinating biology of skin-stage sporozoites and provided additional insights into vaccine-induced protection.


2018 ◽  
Vol 23 (4) ◽  
pp. 397-426 ◽  
Author(s):  
Maral Darouei ◽  
Helen Pluut

PurposeRecent evidence from glass cliff research suggests that women are more willing than men to accept risky leadership positions. The purpose of this paper (based on three studies) is to reveal and resolve the apparent paradox that women are more risk averse than men yet end up in risky leadership positions.Design/methodology/approachIn Study I, risk attitudes of 125 participants were surveyed to understand gender differences in risk taking. In two experimental vignette studies, 119 university students (Study II) and 109 working adults (Study III) were offered a leadership position in either a risky or successful company and asked to rate their willingness to accept the job.FindingsTogether, the results showed that although women are generally more risk averse than men, women who scored low on career self-efficacy were more likely to perceive a risky job as a promotional opportunity and were therefore more willing to accept such a job. These findings shed light on the role of women’s career decision making in the glass cliff phenomenon.Originality/valueGlass cliff research has focused almost exclusively on organizational decision makers. The authors aim to better understand the glass cliff phenomenon by incorporating the perspective of job seekers.


2020 ◽  
Vol 88 (7) ◽  
Author(s):  
Alexander B. Smith ◽  
Joshua Soto Ocana ◽  
Joseph P. Zackular

ABSTRACT Clostridioides difficile is a Gram-positive, spore-forming, anaerobic bacterium that infects the human gastrointestinal tract, causing a wide range of disorders that vary in severity from mild diarrhea to toxic megacolon and/or death. Over the past decade, incidence, severity, and costs associated with C. difficile infection (CDI) have increased dramatically in both the pediatric and adult populations. The factors driving this rapidly evolving epidemiology remain largely unknown but are likely due in part to previously unappreciated host, microbiota, and environmental factors. In this review, we will cover the risks and challenges of CDI in adult and pediatric populations and examine asymptomatic colonization in infants. We will also discuss the emerging role of diet, pharmaceutical drugs, and pathogen-microbiota interactions in C. difficile pathogenesis, as well as the impact of host-microbiota interactions in the manifestation of C. difficile-associated disease. Finally, we highlight new areas of research and novel strategies that may shed light on this complex infection and provide insights into the future of microbiota-based therapeutics for CDI.


2015 ◽  
Vol 71 (5) ◽  
pp. 1094-1114 ◽  
Author(s):  
Daniel Martínez-Ávila ◽  
Richard Smiraglia ◽  
Hur-Li Lee ◽  
Melodie Fox

Purpose – The purpose of this paper is to discuss and shed light on the following questions: What is an author? Is it a person who writes? Or, is it, in information, an iconic taxonomic designation (some might say a “classification”) for a group of writings that are recognized by the public in some particular way? What does it mean when a search engine, or catalog, asks a user to enter the name of an author? And how does that accord with the manner in which the data have been entered in association with the names of the entities identified with the concept of authorship? Design/methodology/approach – The authors use several cases as bases of phenomenological discourse analysis, combining as best the authors can components of eidetic bracketing (a Husserlian technique for isolating noetic reduction) with Foucauldian discourse analysis. The two approaches are not sympathetic or together cogent, so the authors present them instead as alternative explanations alongside empirical evidence. In this way the authors are able to isolate components of iconic “authorship” and then subsequently engage them in discourse. Findings – An “author” is an iconic name associated with a class of works. An “author” is a role in public discourse between a set of works and the culture that consumes them. An “author” is a role in cultural sublimation, or a power broker in deabstemiation. An “author” is last, if ever, a person responsible for the intellectual content of a published work. The library catalog’s attribution of “author” is at odds with the Foucauldian discursive comprehension of the role of an “author.” Originality/value – One of the main assets of this paper is the combination of Foucauldian discourse analysis with phenomenological analysis for the study of the “author.” The authors turned to Foucauldian discourse analysis to discover the loci of power in the interactions of the public with the named authorial entities. The authors also looked to phenomenological analysis to consider the lived experience of users who encounter the same named authorial entities. The study of the “author” in this combined way facilitated the revelation of new aspects of the role of authorship in search engines and library catalogs.


2014 ◽  
Vol 35 (5) ◽  
pp. 594-612 ◽  
Author(s):  
Chiara Mussida ◽  
Enrico Fabrizi

Purpose – The purpose of this paper is to shed light on transitions from the state of unemployment to that of employment and of inactivity in Italy and Spain. Design/methodology/approach – First, the paper investigates the determinants of unemployment outflows in these two Mediterranean labour markets. Then, the paper examines discrepancies and similarities between specific outflow determinants, especially the interactions between gender and marital status, by comparing results obtained across countries. Findings – The findings of the paper suggest that gender and marital status influence the probability of unemployment outflows in both countries, although not in the same way, especially with reference to marital status. Discrepancies also emerge in relation to the role of geographical area of residence. Originality/value – International comparisons of unemployment outflows are rather new in the literature, and as far as we know none have been performed using European Union Statistics on Income and Living Conditions data. Further, although studies quite often examine the issue of gender-related labour mobility using the European Community Household Panel survey that took place in the 1990s (Arulampalam et al., 2007; Garcia Pérez and Rebollo Sanz, 2005; Theodossiou and Zangelidis, 2009), one of the main contributions of this paper is that it provides a systematic examination of the issue, considering the influence of gender and marital status differences on patterns of unemployment outflows to employment and inactivity.


2018 ◽  
Vol 200 (18) ◽  
Author(s):  
James A. Budnick ◽  
Lauren M. Sheehan ◽  
Lin Kang ◽  
Pawel Michalak ◽  
Clayton C. Caswell

ABSTRACTElucidating the function of proteins <50 amino acids in length is no small task. Nevertheless, small proteins can play vital roles in the lifestyle of bacteria and influence the virulence of pathogens; thus, the investigation of the small proteome is warranted. Recently, our group identified theBrucella abortusprotein VtlR as a transcriptional activator of four genes, one of which is the well-studied small regulatory RNA AbcR2, while the other three genes encode hypothetical small proteins, two of which are highly conserved among the orderRhizobiales. This study provides evidence that all three genes encode authentic small proteins and that all three are highly expressed under oxidative stress, low-pH, and stationary-phase growth conditions. Fractionation of the cells revealed that the proteins are localized to the membranes ofB. abortus. We demonstrate that the small proteins under the transcriptional control of VtlR are not accountable for attenuation observed with theB. abortusvtlRdeletion strain. However, there is an association between VtlR-regulated genes and growth inhibition in the presence of the sugarl-fucose. Subsequent transcriptomic analyses revealed thatB. abortusinitiates the transcription of a locus encoding a putative sugar transport and utilization system when the bacteria are cultured in the presence ofl-fucose. Altogether, our observations characterize the role of the VtlR-controlled small proteins BAB1_0914, BAB2_0512, and BAB2_0574 in the biology ofB. abortus, particularly in the capacity of the bacteria to utilizel-fucose.IMPORTANCEDespite being one of the most common zoonoses worldwide, there is currently no human vaccine to combat brucellosis. Therefore, a better understanding of the pathogenesis and biology ofBrucellaspp., the causative agent of brucellosis, is essential for the discovery of novel therapeutics against these highly infectious bacteria. In this study, we further characterize the virulence-associated transcriptional regulator VtlR inBrucella abortus. Our findings not only shed light on our current understanding of a virulence related genetic system inBrucellaspp. but also increase our knowledge of small proteins in the field of bacteriology.


2016 ◽  
Vol 33 (3) ◽  
pp. 182-192 ◽  
Author(s):  
Juha Munnukka ◽  
Outi Uusitalo ◽  
Hanna Toivonen

Purpose Advertisers use various tactics to influence consumer purchases and create positive associations with their brands. The purpose of this study is to explore the formation of peer-endorser credibility and its influence on attitude formation. The role of product involvement in the formation of attitudes and endorser credibility is also examined. Design/methodology/approach A quantitative study was conducted among university students. Data were collected using an online questionnaire concerning three advertisements for which identical questionnaires were constructed; 364 responses were generated. Findings The authors show that the credibility of a peer endorser is constructed from trustworthiness, expertise, similarity and attractiveness dimensions that positively affect consumers’ attitude toward an advertisement and a brand. Product involvement affects advertising effectiveness indirectly through the endorser-credibility construct. Finally, the authors show that a consumer’s experience with an advertised product affects the perception of endorser credibility and the effectiveness of the advertisement. Originality/value The findings reveal new insights into the little studied area of peer-endorser effectiveness. The authors shed light on the construction of peer endorser credibility and the relative importance of specific credibility dimensions on the effectiveness of an advertisement. This study also provides information on the direct and indirect effects of consumers’ brand involvement on attitudes toward advertisements.


2016 ◽  
Vol 54 (2) ◽  
pp. 270-287 ◽  
Author(s):  
Catharina von Koskull ◽  
Tore Strandvik ◽  
Bård Tronvoll

Purpose – The purpose of this paper is to shed light on an aspect of service innovation processes that has remained fairly hidden so far, namely, the role of emotions. Design/methodology/approach – The authors use the strategizing approach from strategy research, which focusses on detailed processes, practices, and discourse, to understand the influence of emotions on service innovation processes. The empirical data stem from a longitudinal ethnographic study of a service innovation process. Findings – In the investigated case, the dominant emotion of anxiety is revealed. The authors focus on this emotion in order to explore how it affects the innovation process itself and the outcome. The authors identify five emotion-driven practices that form elements of what the authors label emotional strategizing. Practical implications – Emotion seems to give energy and direction to the service innovation process. This is both positive and challenging for top-level managers. Originality/value – The authors reveal a hidden aspect of service innovation processes – the effect of emotions. Furthermore, the authors show that emotions are important because they give energy and direction to the innovation work, and emerge in practices. Emotional strategizing, as a new term, gives visibility to this important issue.


1998 ◽  
Vol 89 (4) ◽  
pp. 559-567 ◽  
Author(s):  
Richard S. Polin ◽  
Murad Bavbek ◽  
Mark E. Shaffrey ◽  
Kevin Billups ◽  
Christopher A. Bogaev ◽  
...  

Object. The goal of this study was to explore whether the levels of soluble adhesion molecules were elevated in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH). This association was suggested by the known inflammatory response in vasospasm and the role of vascular adhesion molecules in regulating leukocytic adhesion to, and migration across, vascular endothelium. Methods. A prospective analysis was performed on CSF samples obtained in 17 patients who had suffered a recent aneurysmal SAH and in 16 control patients by using quantitative enzyme-linked immunosorbent assays for E-selectin, intercellular adhesion molecule—1 (ICAM—1), vascular adhesion molecule—1 (VCAM-1), and L-selectin. Levels of soluble forms of E-selectin (p = 0.0013), ICAM-1 (p = 0.0001), and VCAM-1 (p = 0.048) were found to be elevated in the CSF of patients after SAH compared with levels in the CSF of normal controls, patients with unruptured aneurysms, and patients tested months after SAH occurred. In addition, individual patients tested at the time of their initial ictus demonstrated a fall in adhesion molecule levels over time. Levels of E-selectin (p = 0.044) were highest in patients who later developed moderate or severe vasospasm. Conclusions. Adhesion molecules are known to be involved in white cell adherence to the endothelium and subsequent diapedesis and migration in which a role in initiation of tissue damage is postulated. The authors have demonstrated the elevation of three adhesion molecules, with severely elevated levels of E-selectin seen in patients who later develop vasospasm. A correlation with a role of vascular adhesion molecules in the pathogenesis of cerebral vasospasm is suggested.


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